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3D chromatin architecture and epigenetic regulation in cancer stem cells

Protein & Cell 2021年第6期12卷 440-454页

作者： Yuliang Feng xingguo liu Siim Pauklin Botnar Research Centre Nuffield Department of OrthopaedicsRheumatology and Musculoskeletal Sciences Old RoadUniversity of OxfordOxford OX37LDUK Guangzhou Regenerative Medicine and Health Guangdong Laboratory CAS Key Laboratory of Regenerative BiologyJoint School of Life SciencesHefei Institute of Stem Cell and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China

Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer *** this process,a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early *** characteristics allow these cancer stem cells(CSCs)to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer *** development and progression are demarcated by transcriptional *** this article,we explore the epigenetic mechanisms shaping gene expression during tumorigenesis and cancer stem cell formation,with an emphasis on 3D chromatin *** the pluripotent stem cell state and epigenetic reprogramming to dedifferentiation in cellular transformation provides intriguing insight to chromatin *** suggest that the 3D chromatin architecture could be used as a target for re-sensitizing cancer stem cells to therapeutics.

关键词： chromatin architecture 3D chromatin topology epigenetics tumorigenesis cancer stem cells pluripotent stem cells

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Epigenome-Metabolome-Epigenome signaling cascade in cell biological processes

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Journal of Genetics and Genomics 2022年第4期49卷 279-286页

作者： Linpeng Li Keshi Chen Yi Wu Ge Xiang xingguo liu CAS Key Laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Medical UniversityGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesGuangzhouGuangdong 510530China c Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

Cell fate determination as a fundamental question in cell biology has been extensively studied at different regulatory levels for many ***,the mechanisms of multilevel regulation of cell fate determination remain ***,we have proposed an Epigenome-Metabolome-Epigenome(E-M-E)signaling cascade model to describe the cross-over cooperation during mouse somatic cell *** this review,we summarize the broad roles of E-M-E signaling cascade in different cell biological processes,including cell differentiation and dedifferentiation,cell specialization,cell proliferation,and cell pathologic *** E-M-E signaling cascades are critical in these cell biological processes,and it is of worth to explore each step of E-M-E signaling cascade.E-M-E signaling cascade model sheds light on and may open a window to explore the mechanisms of multilevel regulation of cell biological processes.

关键词： Cell biological processes Chromatin Epigenome Metabolome Signaling cascade

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Multi-phase separation in mitochondrial nucleoids and eukaryotic nuclei

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Biophysics Reports 2023年第3期9卷 113-119页

作者： Qi Long Yanshuang Zhou Jingyi Guo Hao Wu xingguo liu CAS Key Laboratory of Regenerative Biology Joint School of Life Sciences The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan People's Hospital Guangzhou Medical University Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine China-New Zealand Joint Laboratory on Biomedicine and Health CUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative Medicine Institute for Stem Cell and Regeneration Institute for Stem Cell and Regeneration Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Centre for Regenerative Medicine and Health Hong Kong Institute of Science & Innovation Chinese Academy of Sciences

In mammalian cells, besides nuclei, mitochondria are the only semi-autonomous organelles possessing own DNA organized in the form of nucleoids. While eukaryotic nuclear DNA compaction, chromatin compartmentalization and transcription are regulated by phase separation, our recent work proposed a model of mitochondrial nucleoid self-assembly and transcriptional regulation by multi-phase separation. Herein, we summarized the phase separation both in the nucleus and mitochondrial nucleoids,and did a comparison of the organization and activity regulating, which would provide new insight into the understanding of both architecture and genetics of nucleus and mitochondrial nucleoids.

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Effects of Er on the microstructure and properties of AZ31 magnesium alloy prepared via the EMS process

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Rare Metals 2010年第4期29卷 339-345页

作者： MA Yutao,ZHANG xingguo,liu Hongbin,and MENG Linggang School of Materials Science and Engineering,Dalian University of Technology,Dalian 116023,China School of Materials Science and Engineering Dalian University of Technology Dalian China

The effects of small amounts of the rare-earth element erbium on the microstructure and the mechanical properties of AZ31 magnesium alloy via the electromagnetic stirring （EMS） process have been studied. It has been shown that AZ31-Er alloys are mainly composed of α-Mg solid solution and β-Mg17TA112 phases. When the Er content reaches 0.12 wt.%, the characteristic peaks of A12Er can be observed. The micro- structure is obviously refined and the tensile strength of the AZ31-based alloy at ambient temperature is significantly improved by contents of 0.03 wt.% Er, especially the elongation （8= 19%）. More addition of Er obviously decreases the tensile strength and elongation of the AZ31-based alloy because of the grain coarsening and the reduction of β-Mg17A112 phases.

关键词： AZ31 magnesium alloy microstructure mechanical properties erbium

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MSC-mediated mitochondrial transfer restores mitochondrial DNA and function in neural progenitor cells of Leber’s hereditary optic neuropathy

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Science China(Life Sciences) 2024年第11期67卷 2511-2519页

作者： Rui Wang Feixiang Bao Manjiao Lu Xiaoyun Jia Jiahui Xiao Yi Wu Qingjiong Zhang xingguo liu Joint School of Life Sciences Guangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences/Guangzhou Medical UniversityGuangzhou 510530China Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong 99077China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou 510530China State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060China University of Chinese Academy of Sciences Beijing 100049China

Leber’s hereditary optic neuropathy(LHON)is a debilitating mitochondrial disease associated with mutations in mitochondrial DNA(mtDNA).Unfortunately,the available treatment options for LHON patients are limited due to challenges in mitochondrial *** our study,we reprogramming LHON urine cells into induced pluripotent stem cells(iPSCs)and differentiating them into neural progenitor cells(NPCs)and neurons for disease *** research revealed that LHON neurons exhibited significantly higher levels of mtDNA mutations and reduced mitochondrial function,confirming the disease ***,through co-culturing LHON iPSC-derived NPCs with mesenchymal stem cells(MSCs),we observed a remarkable rescue of mutant mtDNA and a significant improvement in mitochondrial metabolic function in LHON *** findings suggest that co-culturing with MSCs can enhance mitochondrial function in LHON NPCs,even after their differentiation into *** discovery holds promise as a potential therapeutic strategy for LHON patients.

关键词： mitochondria mitochondrial DNA mitochondrial diseases induced pluripotent stem cells stem cells metabolism energy mesenchymal stem cells

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Current approaches to reduce or eliminate mitochondrial DNA mutations

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Science China(Life Sciences) 2016年第5期59卷 532-535页

作者： Liang Yang Tingfang Mei Xiaobing Lin Haite Tang Yi Wu Rui Wang Jinglei liu Zahir Shah xingguo liu Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences

Mitochondrial DNA （mtDNA） mutations have been impli- cated in a broad range of disorders which severely affect human health （Wallace, 1999）. Some drugs have been developed to slow down pathological changes of mitochon- drial disorders. However, there is no effective treatment for patients with mtDNA mutations, mtDNA is less protected and has fewer repair mechanisms than nuclear DNA （nDNA）. Such a reality results in a much higher mutation rate in mtDNA than that in nDNA. The mixture of mutated mtDNA versus wild-type mtDNA is known as hetero- plasmy. Mitochondrial threshold effect refers to the fact that mtDNA mutation must accumulate to high proportions （60%-90%） before respiratory activity is affected （Schon et al., 2012）. It is feasible to selectively reduce the levels of mu- tated mtDNA while sparing wild-type mtDNA to skew this ratio back to a healthier range. Here, we describe the link between mtDNA mutation and mitochondrial diseases, and we summarize several newly developed approaches with regard to the reduction or elimination of mtDNA mutation in mammals. These methods include nuclear gene modula- tion, molecular approaches targeting mutated mtDNA, mtDNA replacement, and induced pluripotent stem cell （iPSC） modeling. These various methods have their own advantages and limitations.

关键词：线粒体DNA突变基因突变 mtDNA突变线粒体疾病人类健康核DNA 多能干细胞病理变化

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Organoids as preclinical models of human disease:progress and applications

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Medical Review 2024年第2期4卷 129-153页

作者： Baodan Chen Cijie Du Mengfei Wang Jingyi Guo xingguo liu CAS Key Laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Guangdong-Hong Kong Joint Laboratory for Stem Cell and Regenerative MedicineChina-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineGIBH-HKU Guangdong-Hong Kong Stem Cell and Regenerative Medicine Research CentreInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouChina University of Chinese Academy of Sciences BeijingChina Innovation Centre for Advanced Interdisciplinary Medicine The Fifth Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

In the field of biomedical research,organoids represent a remarkable advancement that has the potential to revolutionize our approach to studying human diseases even before clinical *** are essentially miniature 3D models of specific organs or tissues,enabling scientists to investigate the causes of diseases,test new drugs,and explore personalized medicine within a controlled laboratory *** the past decade,organoid technology has made substantial progress,allowing researchers to create highly detailed environments that closely mimic the human *** organoids can be generated from various sources,including pluripotent stem cells,specialized tissue cells,and tumor tissue *** versatility enables scientists to replicate a wide range of diseases affecting different organ systems,effectively creating disease replicas in a laboratory *** exciting capability has provided us with unprecedented insights into the progression of diseases and how we can develop improved *** this paper,we will provide an overview of the progress made in utilizing organoids as preclinical models,aiding our understanding and providing a more effective approach to addressing various human diseases.

关键词： organoids human disease regenerative medicine drug screening tumor

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Mitochondria as multifaceted regulators of ferroptosis

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Life Metabolism 2022年第2期1卷 134-148页

作者： Jingyi Guo Yunhao Zhou Dingfei liu Mengfei Wang Yi Wu Daolin Tang xingguo liu CAS Key Laboratory of Regenerative Biology Joint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhouGuangdong 510530China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine China-New Zealand Joint Laboratory on Biomedicine and HealthCUHK-GIBH Joint Research Laboratory on Stem Cells and Regenerative MedicineInstitute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China University of Chinese Academy of Sciences Beijing 100093China Department of Surgery UT Southwestern Medical CenterDallasTXUSA Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong KongChina

Mitochondria are well known to be“energy factories”of the cell as they provide intracellular ATP via oxidative ***,they also function as a“cellular suicidal weapon store”by acting as a key mediator of various forms of regulated cell death,including apoptosis,pyroptosis,necroptosis,and ***,distinct from the other types of regulated cell death,is characterized by iron-dependent lipid peroxidation and subsequent plasma membrane *** evidence suggests that an impaired ferroptotic response is implicated in various diseases and pathological conditions,and this impaired response is associated with dramatic changes in mitochondrial morphology and *** are the center of iron metabolism and energy production,leading to altered lipid peroxidation *** a growing number of studies have explored the inextricable link between mitochondria and ferroptosis,the role of this organelle in regulating ferroptosis remains ***,we review recent advances in our understanding of the role of mitochondria in ferroptosis and summarize the characteristics of this novel iron-based cellular suicide weapon and its *** also discuss the importance of ferroptosis in pathophysiology,including the need for further understanding of the relationship between mitochondria and ferroptosis to identify combinatorial targets that are essential for the development of successful drug discovery.

关键词： mitochondria ferroptosis lipid peroxidation iron ROS

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Short-form OPA1 is a molecular chaperone in mitochondrial intermembrane space

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Science China(Life Sciences) 2022年第2期65卷 227-235页

作者： Deyang Yao Yukun Li Sheng Zeng Zhifan Li Zahir Shah Bigui Song Jinglei liu Yi Wu Liang Yang Qi Long Wenqian Wang Zhijuan Hu Haite Tang xingguo liu School of Life Sciences University of Science and Technology of ChinaHefei 230027China Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) CAS Key Laboratory of Regenerative BiologyJoint School of Life SciencesGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhou Medical UniversityGuangzhou 510530China Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine Institute for Stem Cell and RegenerationGuangzhou Institutes of Biomedicine and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesGuangzhou 510530China Centre for Regenerative Medicine and Health Hong Kong Institute of Science&InnovationChinese Academy of SciencesHong Kong SARChina

Mitochondria,double-membrane organelles,are known to participate in a variety of metabolic and signal transduction *** intermembrane space(IMS)of mitochondria is proposed to subject to multiple damages emanating from the respiratory *** optic atrophy 1(OPA1),an important protein for mitochondrial fusion,is cleaved into soluble short-form(S-OPA1)under *** we report that S-OPA1 could function as a molecular chaperone in *** purified the S-OPA1(amino acid sequence after OPA1 isoform 5 S1 site)protein and showed it protected substrate proteins from thermally and chemically induced aggregation and strengthened the thermotolerance of Escherichia coli(***).We also showed that S-OPA1 conferred thermotolerance on IMS proteins,e.g.,*** chaperone activity of S-OPA1 may be required for maintaining IMS homeostasis in mitochondria.

关键词： mitochondria OPA1 chaperone mitochondrial homeostasis heat shock

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Choosing proper fluorescent dyes, proteins, and imaging techniques to study mitochondrial dynamics in mammalian cells

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Biophysics Reports 2017年第Z2期3卷 64-72页

作者： xingguo liu Liang Yang Qi Long David Weaver Gy?rgy Hajnóczky Key Laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of Sciences Department of Pathology Mito Care CenterAnatomy and Cell BiologyThomas Jefferson University

Mitochondrial dynamics refers to the processes maintaining mitochondrial homeostasis, including mitochondrial fission, fusion, transport, biogenesis, and mitophagy. Mitochondrial dynamics is essential for maintaining the metabolic function of mitochondria as well as their regulatory roles in cell *** this review, we summarize the recently developed imaging techniques for studying mitochondrial dynamics including: mitochondrial-targeted fluorescent proteins and dyes, live-cell imaging using photoactivation, photoswitching and cell fusion, mitochondrial transcription and replication imaging by in situ hybridization, and imaging mitochondrial dynamics by super-resolution microscopy. Moreover,we discuss examples of how to choose and combine proper fluorescent dyes and/or proteins.

关键词： Imaging Mitochondrial dynamics Photoactivation Photoswitching Super-resolution microscope

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